In the brain, one period of extreme vulnerability to external influences like our diet, occurs before we even have control over what we eat. That is to say, our mother’s nutritional and metabolic status can influence the proper development of the brain itself. It has been shown that maternal obesity and excessive maternal weight gain can lead to an elevated risk of type-2-diabetes and obesity in children. However, even more surprising is the correlation between maternal metabolic status and the risk of the development of cognitive diseases such as ADHD. With a recent study assessing one million human births showing that more than 50 percent of women in the USA and Europe surpass the recommended body weight guidelines during pregnancy, the effect of this altered maternal nutrition on the baby’s brain needs to be understood (Goldstein RF et al. BMC Med 2018).

The melanocortin system is a component of the circuitry that is required for normal energy balance and that is perturbed in the energy-regulating center of the brain, called the hypothalamus. This system consists of multiple proteins, called G-protein coupled receptors, as well as associated peptides which increase or decrease their function, namely agouti-related peptide (AgRP) and proopiomelanocortin (POMC). Genetic mutations in parts of this system result in extreme obesity in humans. Interestingly, previous work in rodent models has shown that maternal high fat diet can negatively regulate the connectivity and function of this melanocortin circuitry within the hypothalamus of the developing offspring . More recent work, has also linked the melanocortin system itself with neuronal networks involved in reward and addiction.

Therefore, to further our understanding of brain circuitry involved in energy balance, specifically with respect to food intake, glucose homeostasis and related behaviors, our projects will focus on three main themes: 

• The role of the melanocortin system in brain regions outside of the hypothalamus
• The consequences to the developing brain due to insults (such as an unhealthy diet) during pregnancy
• The long-term effects of maternal malnutrition on the development of the offspring

Any inquiries releted to these topics can be sent directly to  Dr. Rachel Lippert.

Dr. Rachel Lippert is leading the newly created Junior Research Group NDF at DIfE as part of the NeuroCure Cluster of Excellence in the neurosciences at Charité - Universitätsmedizin Berlin. The Cluster is funded since 2007 by the German federal and state governments, receiving further funding within the Excellence Strategy since 2019. The focus of this interdisciplinary research network is on investigating neurological and psychiatric disorders. Central aim is to better understand disease mechanisms and to develop new therapies. Fostering local networks of scientists and their research activities is an important part of the Cluster’s efforts. In addition, NeuroCure has established a significant number of new research groups as well as several technological platforms. In 2019, the DIfE became cooperation partner of the cluster.

Gil, C. I., Coull, B. M., Jonas, W., Lippert, R., Ost, M., Klaus, S.: Mitochondrial stress-induced GDF15-GFRAL axis promotes anxiety-like behavior and CRH-dependent anorexia. Life Science Alliance 5(11):e202201495 (2022). [Open Access]

Bedenbaugh, M. N., Brener, S. C., Maldonado, J., Lippert, R. N., Sweeney, P., Cone, R. D., Simerly, R. B.: Organization of neural systems expressing melanocortin-3 receptors in the mouse brain: Evidence for sexual dimorphism. J. Comp. Neurol. 530(16), 2835-2851 (2022).

Lam, B. Y. H., Williamson, A., Finer, S., Day, F. R., Tadross, J. A., Gonçalves Soares, A., Wade, K., Sweeney, P., Bedenbaugh, M. N., Porter, D. T., Melvin, A., Ellacott, K. L. J., Lippert, R. N., Buller, S., Rosmaninho-Salgado, J., Dowsett, G. K. C., Ridley, K. E., Xu, Z., Cimino, I., Rimmington, D., Rainbow, K., Duckett, K., Holmqvist, S., Khan, A., Dai, X., Bochukova, E. G., Trembath, R. C., Martin, H. C., Coll, A. P., Rowitch, D. H., Wareham, N. J., van Heel, D. A., Timpson, N., Simerly, R. B., Ong, K. K., Cone, R. D., Langenberg, C., Perry, J. R. B., Yeo, G. S., O’Rahilly, S.: MC3R links nutritional state to childhood growth and the timing of puberty. Nature 599, 436–441 (2021). [Open Access]

Lippert, R. N., Brüning, J. C.: Maternal metabolic programming of the developing central nervous system – unified pathways to metabolic and psychiatric disorders. Biol. Psychiatry 91(10), 898-906 (2022). [Open Access]